A combination of virologic, genetic, and biochemical approaches is being used to study the natural history of murine leukemia virus (MuLV) infection. Following the plan of previous genetic studies, which delineated two virus-inducing loci in the high ecotropic virus, high leukemia AKR strain of mice, mouse strains selected for interesting biological characteristics (e.g., NZB, a high producer of xenotropic virus; B10.Br/Li, which is chemically inducible for both N- and B-tropic ecotropic virus; RF/J and PL, high ecotropic virus strains) are being appropriately mated with phenotypically defined mouse strains and the hybrids tested for MuLV production and/or virus inducible by IUDR treatment. The several studies underway are expected to answer the question of whether a single gene region can code for more than one virus genotype, may permit mapping of virus loci in additional mouse strains, and could yield information about the relation of xenotropic virus to spontaneous disease. Nucleic acid hybridization techniques are being used for unique and common viral DNA sequences Methods for producing and quantitating phenotypic mixtures of ecotropic and xenotropic MuLV have been developed. Two apparently new host range variants of MuLV have been detected in wild mice, and studies of the pathogenesis of wild mouse ecotropic and amphotropic viruses are in progress.